INT102448

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Context Info
Confidence 0.75
First Reported 2001
Last Reported 2008
Negated 0
Speculated 2
Reported most in Body
Documents 23
Total Number 26
Disease Relevance 4.62
Pain Relevance 10.90

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

protein transporter activity (RAMP1) extracellular space (RAMP1) plasma membrane (RAMP1)
Anatomy Link Frequency
trigeminal ganglion 1
brain 1
RAMP1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Calcitonin gene-related peptide 3667 99.70 Very High Very High Very High
Neuropeptide 564 99.44 Very High Very High Very High
trigeminal ganglion 26 99.16 Very High Very High Very High
Potency 254 97.20 Very High Very High Very High
Inflammation 3 95.68 Very High Very High Very High
Chronic pancreatitis 6 95.56 Very High Very High Very High
antagonist 205 95.44 Very High Very High Very High
agonist 205 88.64 High High
medulla 4 85.72 High High
Migraine 105 81.96 Quite High
Disease Link Frequency Relevance Heat
Pancreatic Cancer 14 99.84 Very High Very High Very High
Ganglion Cysts 26 98.72 Very High Very High Very High
Adenocarcinoma 12 96.64 Very High Very High Very High
Neurogenic Inflammation 2 96.12 Very High Very High Very High
Pancreatitis 6 95.56 Very High Very High Very High
Disease 55 91.76 High High
Hypoxia 6 91.20 High High
Headache 103 81.96 Quite High
Stroke 18 67.88 Quite High
INFLAMMATION 1 65.60 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
All 5 evaluated pancreatic cancer cells lines expressed ADM, CRLR, RAMP1 and RAMP2, whereas RAMP3 was expressed in only 1/5 pancreatic cancer cell lines.
Gene_expression (expressed) of RAMP1 associated with pancreatic cancer
1) Confidence 0.75 Published 2007 Journal Int. J. Cancer Section Abstract Doc Link 17290391 Disease Relevance 1.61 Pain Relevance 0.27
By immunohistochemistry, ADM, CRLR, RAMP1 and RAMP2, but not RAMP3, were expressed in pancreatic cancer cells.
Gene_expression (expressed) of RAMP1 associated with pancreatic cancer
2) Confidence 0.75 Published 2007 Journal Int. J. Cancer Section Abstract Doc Link 17290391 Disease Relevance 1.13 Pain Relevance 0.25
It was proposed that elevated RAMP1 expression could sensitize the trigeminal ganglion of individuals to CGRP actions such as CGRP release and neurogenic inflammation [47].
Gene_expression (expression) of RAMP1 in trigeminal ganglion associated with ganglion cysts, inflammation, trigeminal ganglion, neurogenic inflammation and calcitonin gene-related peptide
3) Confidence 0.67 Published 2008 Journal J Headache Pain Section Body Doc Link PMC2245994 Disease Relevance 0.50 Pain Relevance 0.94
Co-expression of CLR with RAMP1 composes the CGRP receptor, while co-expression of CLR with either RAMP2 or RAMP3 represents the adrenomedullin (AM) receptor or possibly a combined receptor (CGRP and AM).
Gene_expression (expression) of RAMP1 associated with calcitonin gene-related peptide
4) Confidence 0.67 Published 2008 Journal J Headache Pain Section Body Doc Link PMC2245994 Disease Relevance 0.60 Pain Relevance 1.16
CGRP receptor belongs to the calcitonin receptor like receptor (CRLR) family of G-protein-coupled receptors and has been shown to require a single transmembrane domain protein called receptor activity modifying protein-1 (RAMP1) for its functional expression as well as activity.
Gene_expression (expression) of RAMP1
5) Confidence 0.61 Published 2001 Journal ScientificWorldJournal Section Abstract Doc Link 14532375 Disease Relevance 0.32 Pain Relevance 0.32
The potency of CGRP to generate cAMP in these cells transfected with the wild type receptor (1.6 ± 0.1 nM, n = 3) was not significantly different from HEK293T-RAMP1 cells expressing the L24A (1.5 ± 0.4 nM, n = 3), L34A (2.0 ± 0.5 nM, n = 3) or double L24A,L34A (1.3 ± 0.2 nM, n = 3) CLR mutants.
Gene_expression (expressing) of HEK293T-RAMP1 associated with calcitonin gene-related peptide and potency
6) Confidence 0.55 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.48
Neuropeptide activation of endogenously expressed CLR-RAMP1 heterodimers has been shown to generate increases in cAMP [9].
Gene_expression (expressed) of RAMP1 associated with neuropeptide
7) Confidence 0.55 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.55
HEK293T stably transfected with RAMP1 was a gift kindly provided by Michel Bouvier (University of Montreal, Quebec, Canada). cAMP Biotrak enzyme-linked immunoassay was purchased from Amersham Biosciences (Piscataway, NJ).
Gene_expression (transfected) of RAMP1
8) Confidence 0.55 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0.07 Pain Relevance 0.37
CLR negative HEK293T cells stably transfected with RAMP1 were propagated in DMEM plus 10% FBS under standard cell culture conditions.
Gene_expression (transfected) of RAMP1
9) Confidence 0.55 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0
Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP).
Spec (determined) Gene_expression (coexpression) of activity-modifying protein associated with neuropeptide
10) Confidence 0.55 Published 2002 Journal J. Cereb. Blood Flow Metab. Section Abstract Doc Link 11973435 Disease Relevance 0 Pain Relevance 0.22
Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP).
Spec (determined) Gene_expression (coexpression) of RAMP associated with neuropeptide
11) Confidence 0.55 Published 2002 Journal J. Cereb. Blood Flow Metab. Section Abstract Doc Link 11973435 Disease Relevance 0 Pain Relevance 0.22
Specific to the CLR, deletion of an 18 amino acid region of the receptor N-terminal domain resulted in a significant loss of 125I-CGRP binding when co-expressed in mammalian cells with RAMP1 [26].
Gene_expression (expressed) of RAMP1 associated with calcitonin gene-related peptide
12) Confidence 0.48 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.42
There was a significant affinity loss of the C-terminal amidated ligand, CGRP(1–36), for the wild type CLR transiently expressed on HEK293T-RAMP1 membranes when compared to the Ki of CGRP for the same receptor (Table 1).
Gene_expression (expressed) of HEK293T-RAMP1 associated with calcitonin gene-related peptide
13) Confidence 0.48 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.42
Analogous saturation binding experiments were performed for the L24A, L34A and L24A,L34A CLR double mutant transiently expressed individually on HEK293T-RAMP1 membranes with an approximate 10-fold decrease in the [125I-Tyr]CGRP(8–37) Kd value calculated for all receptor mutations (Table 1).
Gene_expression (expressed) of HEK293T-RAMP1 associated with calcitonin gene-related peptide
14) Confidence 0.48 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.34
Previous studies on the calcitonin-like receptor (CLR), which requires co-expression of the receptor-activity-modifying protein-1 (RAMP1) to function as a CGRP receptor, have shown an 18 amino acid N-terminus sequence important for binding CGRP.
Gene_expression (expression) of RAMP1 associated with calcitonin gene-related peptide
15) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Abstract Doc Link PMC1525162 Disease Relevance 0.09 Pain Relevance 0.43
However, this affinity loss was no different from wild type receptor when CGRP(1–36) or CGRP(1–19) were used to compete for specific L24A, L34A or L24A,L34A mutant CLR binding sites on transiently transfected HEK293T-RAMP1 cells.
Gene_expression (transfected) of HEK293T-RAMP1 associated with calcitonin gene-related peptide
16) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.51
From the best fit curve, EC50 and Ki values were calculated and compared between wild type and mutant CGRP receptors from concomitantly transfected HEK293T-RAMP1 cells.
Gene_expression (transfected) of HEK293T-RAMP1 associated with calcitonin gene-related peptide
17) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.08
Increasing amounts of CGRP(1–36) was able to generate cAMP in HEK293T-RAMP1 cells transiently expressing the wild type CLR in a concentration-dependent manner (Fig 4B) The EC50 of CGRP(1–36) for the expressed wild type CLR-RAMP1 heterodimer was calculated to be 4.3 ± 0.8?
Gene_expression (expressed) of RAMP1 associated with calcitonin gene-related peptide
18) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.57
Previous investigations have identified [125I-Tyr]CGRP(8–37) as a selective high affinity radioligand for mature CGRP receptors (i.e., CLR-RAMP1 heterodimers) endogenously expressed in rat brain and peripheral tissues [27].
Gene_expression (expressed) of RAMP1 in brain associated with calcitonin gene-related peptide
19) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.46
For both CGRP(1–36) or CGRP(1–19) there was a concentration-dependent increase in the amount of cAMP produced from HEK293T-RAMP1 cells transiently expressing the wild type CLR (Table 2).
Gene_expression (expressing) of HEK293T-RAMP1 associated with calcitonin gene-related peptide
20) Confidence 0.43 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.80

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